Hemodialysis-related portosystemic encephalopathy (HRPSE) is a clinical phenomenon where portosystemic encephalopathy (PSE) develops without liver dysfunction, usually caused by changes in the portosystemic blood flow related to hemodialysis. We describe the case of a 22-year old patient with a transjugular intrahepatic portosystemic shunt (TIPS) who developed HRPSE several months after initiation of hemodialysis. Despite initial therapy with laxatives and neomycin symptoms recurred. It was only after relocation of the hemodialysis catheter from the superior caval vein to the femoral vein that symptoms completely resolved.

Hepatic encephalopathy is a reversible progressive neuropsychiatric disorder that encompasses a wide clinical spectrum. Covert hepatic encephalopathy is defined as patients with minimal hepatic encephalopathy and Grade I encephalopathy by West-Haven Criteria. Terminology such as "sub-clinical", "latent", and "minimal" appear to trivialize the disease and have been replaced by the term covert. The lack of clinical signs means that covert hepatic encephalopathy is rarely recognized or treated outside of clinical trials with options for therapy based on patients with episodic hepatic encephalopathy. This review discusses the current available options for therapy in covert hepatic encephalopathy and focuses on non-absorbable disacharides (lactulose or lactitol), antibiotics (rifaximin), probiotics/synbiotics and l-ornithine-l-aspartate.

Minimal hepatic encephalopathy (mHE) consists of cognitive deficits found on neuropsychological and/or neurophysiologic methods in patients with liver disease, present most commonly in cirrhosis. Patients suffering from mHE may have psychomotor slowing and cognitive deficits affecting their ability to perform many activities of daily life, especially driving and other activities requiring subtle cognitive abilities. It has been now been shown that patients with mHE improve after treatment with agents like lactulose and other therapeutic interventions. Neuropsychological and neurophysiologic tests have been widely used and have shown the greatest promise for the detection of mHE. Commonly used psychometric tests include trailmaking tests (number and figure connection tests) and Wechsler Adult Intelligence Scale (WAIS) for verbal and performance skills. Among the various neuropsychological or psychometric tests, trailmaking tests and block design and digit symbol tests from WAIS-performance battery appear to be adequate for diagnosis of mHE. Standardized tests including NCT A and B, line tracing, serial dotting test and digits-symbol test (PSE syndrome test) validated in German patients need validation in other populations. Both exogenous evoked potentials and endogenous event-related potentials have been used extensively in diagnosing mHE. However, the event-related P300 wave is the most consistent wave and can be considered the electrophysiological counterpart of the psychometric tests as both involve active use of the cognitive faculties. Other new tests like the critical flicker frequency have shown some promise but further studies are required to substantiate initial results. In conclusion, a combination of at least two psychometric (trailmaking tests [NCT or FCT], block design and digit symbol test) and neurophysiological tests (P300 auditory evoked potential or electroencephalography with mean dominant frequency) appears to be optimal in detecting mHE.

A case of PI in a 57-year-old patient with colonic inertia treated with lactulose for PSE secondary to cirrhosis is described. The colonic inertia led to longer transit time. Retained lactulose and a build-up of carbon dioxide and hydrogen gas occurred in the setting of altered bacterial flora deficient in hydrogen metabolism. The increased gas pressure caused extravasation of air into the intestine, causing PI with pneumoperitoneum. They both resolved with discontinuation of lactulose.

Lactose intolerance occurs in the majority of human groups, excluding people from Northern Europe. Because its effect is similar to that of lactulose, lactose seems to be an alternative treatment for patients with portal-systemic encephalopathy (PSE) and lactase deficiency. The mechanism of action of lactose is similar to that of lactulose. In vivo, lactose improves PSE parameters and causes acidic diarrhea. We performed in vitro studies in a fecal incubation system to investigate the biochemical and bacteriological effects induced by different substances customarily used for the treatment of patients with PSE (lactose, lactulose and Neomycin). In vitro experiments showed that lactose and lactulose decreased aerobic flora counts and reduced the pH of fecal incubation. Both disaccharides reduced the ammonia concentration in the incubation system.

To evaluate the prevalence of latent PSE in unselected ambulatory patients with liver cirrhosis practicing physicians were asked to perform two non instrumental psychometric tests (number connection test and line tracing test) on patients with clinical signs of liver cirrhosis and portal hypertension. Tests were repeated after 8 weeks of treatment with Lactulose in those patients considered to have latent PSE at the initial evaluation. 296 physicians tested a total of 783 patients, 771 of these could be evaluated. 551 patients (71.5%) were considered to have latent PSE. There was a significant correlation between psychometric test results and biochemical parameters related to liver function. Repeat testing after 8 weeks treatment with Lactulose revealed definite improvement of psychometric test results in 88% of the patients. At the final evaluation only about 30% of the patients fulfilled the criteria of latent PSE. There was a statistically significant albeit weak correlation between changes in biochemical parameters and psychometric improvement. Psychometric testing with simple non instrumental tests proved to be practicable in the office setting.

Several toxic factors have been implicated in the pathogenesis of hepatic encephalopathy (PSE) among which ammonia plays a dominant role. More recently, the gamma-aminobutyric acid (GABA) hypothesis in which an increase in the GABA-ergic tone and the presence of one or more GABA/benzodiazepine receptor ligands which interact with that receptor, has been proposed. We investigated the levels of GABA and ammonia in plasma of patients with acute PSE to test the hypothesis that elevated plasma GABA levels would be found in acute encephalopathy and that GABA levels would correlate with the degree of hepatic encephalopathy. We measured plasma levels of GABA and ammonia during an acute episode of PSE, spontaneous or precipitated by gastrointestinal bleeding or sepsis, and performed assessments of PSE by the PSE index. Patients were evaluated before and two days after standard treatment with lactulose. We also measured plasma GABA levels in the hepatic vein of a selected group of patients undergoing hemodynamic studies. Plasma GABA levels were significantly higher in patients with acute PSE (458 +/- 108 pmol/mL) when compared with normal subjects (110 +/- 23 pmol/mL) (p < 0.01) although no correlation was found between plasma GABA concentration and the degree of PSE. Changes in plasma ammonia, however, correlated with improvements in the PSE index (r = 0.56; p < 0.02) and with abnormalities in the EEG (r = 0.65; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy and the tolerability of the new crystalline pure lactulose formulation (Laevolac Cristalli) vs lactitol is evaluated in 40 patients suffering from liver cirrhosis and treated for the associated encephalopathy (PSE). Both disaccharides proved to be effective in the maintenance therapy of PSE. With respect to the previous formulation of lactulose, the crystalline one has a significantly lower incidence of side-effects. Pure crystalline lactulose, showing a similar efficacy and rise of side-effects, proved to be better accepted by the subjects of this study.